Solutions for Pharmaceutical Analysis - Application Notebook

Importance of the Topic

Pharmaceutical analysis demands highly sensitive, selective, and compliant methods to profile lipids, chiral drugs, trace impurities, polymorphs, and elemental contaminants. Advanced analytical platforms ensure product quality, safety, and regulatory compliance worldwide.

Study Objectives and Overview

This compilation of application reports covers:

• Phospholipid profiling via targeted LC-MS/MS MRM libraries and SimLipid software
• MS imaging of drug localization in tissues
• Simultaneous LC-MS/MS quantitation of tyrosine kinase inhibitors in plasma
• Ultra-fast UHPLC methods for pharmacopoeial monographs
• Dual-mode UHPLC/SFC for chiral and impurity analyses
• Online SFE-SFC-PDA for cleaning validation and biomarker extraction
• DSC for polymorphism characterization
• UFPLC for rapid preparative purification
• High-sensitivity GC and GC-MS methods for residual solvents and genotoxic impurities
• ICP-AES for multi-element analysis under ICH Q3D
• Automated data evaluation and reporting with LabSolutions iFlagger and Report Plus

Methodology and Instrumentation

Major techniques and systems include:

• Triple quadrupole LC-MS/MS (LCMS-8050/8060) with MRM libraries
• iMScope TRIO imaging mass microscope
• Prominence/X2 and Nexera-i UHPLC/SFC platforms
• UFPLC preparative LC for high-purity isolation
• Supercritical fluid chromatography (Nexera UC) for chiral screening
• Online SFE-SFC-MS/MS for direct sample extraction
• Shimadzu RID-20A refractive index detector for excipient testing
• GC-2030 GC and GCMS-QP2020 for residual solvent analysis
• ICPE-9820 ICP-AES for elemental impurity quantitation
• LabSolutions software for compliance and report generation

Key Results and Discussion

• Phospholipid MRM profiling detected hundreds of constituents and fatty acid composition in biological samples
• SimLipid software streamlined lipid annotation in control versus treated tissues
• MS imaging localized amiodarone to lung lesions with μm-scale resolution
• LC-MS/MS methods quantified multiple TKIs in plasma with <15% accuracy at LLOQ
• UHPLC replaced HPLC monographs to achieve >10× faster runs and 80% less solvent
• SFC screening optimized chiral separations for omeprazole and imdapamide
• Online SFE-SFC-PDA extracted and quantified cleaning validation swab residues in one run
• UFPLC isolated atorvastatin impurities in 90 min versus 8 h
• DSC characterized drug polymorphs via melting and recrystallization peaks
• GC and HS-GC-FID/MS met USP residual solvent limits with S/N>5 and RSD<2%
• ICP-AES achieved PDE compliance for 24 elemental impurities with LOQs below required limits
• LabSolutions iFlagger automated qualitative flagging and LabSolutions Report Plus generated custom reports

Benefits and Practical Applications

These methods reduce analysis time, lower solvent consumption and operational cost, while maintaining high sensitivity and regulatory compliance for QA/QC in pharmaceutical R&D and manufacturing.

Future Trends and Opportunities

Prospective developments include:

• Integrated multi-omic platforms combining SFC, LC-MS/MS, and imaging
• AI-driven method optimization and data review
• Ambient ionization for direct tissue and solid analysis
• Greater automation for 21 CFR Part 11–compliant audits and reporting

Conclusion

Shimadzu’s advanced instrumentation and software deliver comprehensive, high-throughput, and compliant analytical workflows for diverse pharmaceutical challenges, from lipidomics to impurity control.

References

• ICH Q3D Guideline for Elemental Impurities
• USP General Chapters <467> Residual Solvents, <621> Chromatography
• JP 16th/17th Editions: Pharmacopoeial methods
• LabSolutions Data Integrity Guidance